Helios expression in CD8 T cells is regulated by cell activation 9383

Abstract Description Helios belongs to a family of transcription factors that regulate lymphoid differentiation and function. In thymic-derived FoxP3 regulatory T cells, Helios promotes suppressive function. Previously, Helios has been observed in CD8 T cells rendered tolerant and terminally exhausted. Here we analyzed the signals that regulate Helios expression in CD8 T cells. We mounted an in vitro assay to identify factors that modulate Helios expression. Productive CD8 activation, achieved by high affinity ligands inhibited Helios expression while activation with low-affinity ligands led to robust Helios induction. Preactivation of APCs with LPS impaired Helios induction. We tested the role of IL-2 in the regulation of Helios. IL-2 and other cytokines that signal through the common gamma chain inhibited Helios induction in a dose-respondent manner. Accordingly, IL-2 neutralization led to higher expression of Helios. Inhibition of the IL-2 signaling pathway had an analogous effect. Luciferase reporter assays demonstrated that STAT5 inhibits Helios expression at a transcriptional level. In summary, Helios expression in CD8 T cells is regulated by the strength of TCR signaling and the abundance of IL-2. These results illustrate a novel pathway that may regulate CD8 T cell effector functions. Funding Sources Supported by CONAHCYT-PRONACE: 303067 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)